**1. Introduction**

Cardiovascular disease (CVD) is the number one cause of death globally [1]. High blood pressure, high LDL cholesterol, and smoking are the key risk factors for CVD and about 49% of Americans have at least one of the three [2]. Hypercholesterolemia (hyperlipidemia/hyperlipoproteinemia/or dyslipidemia) is a condition characterized by an elevation of any or all parameters of lipid profile or lipoprotein levels in the blood [3]. Hypercholesterolemia generally means high levels of total cholesterol or LDL-C with normal

Orme-Johnson, D.; Ramaratnam, S.; Schneider, R.H. A Systematic Review and Meta-Analysis of Ayurvedic Herbal Preparations for Hypercholesterolemia. *Medicina* **2021**, *57*, 546. https://doi.org/10.3390/ medicina57060546

Academic Editor: Jimmy T. Efird

Received: 31 March 2021 Accepted: 18 May 2021 Published: 28 May 2021

**Citation:** Gyawali, D.; Vohra, R.;

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

or low levels of HDL-C. The guidelines of National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) suggests LDL-C level < 100 mg/dL, (100–129) mg/dL, (130–159) mg/dL, and >160 as optimal, above optimal, borderline high, and high, respectively. It also suggests that the LDL-C should be the primary target of any cholesterol reducing therapy [4]. As with other types of CVD, genetics, age, and gender are some of the non-modifiable risk factors for hypercholesterolemia. Hypercholesterolemia is one of the most significant contributors to the development of CVD, and if managed properly, is directly responsible for reducing risk of morbidity and mortality associated with CVD [5,6] (The Lipid Research Clinics Coronary Primary Prevention Trial results I and II). The burden of hypercholesterolemia is also reflected by recurring acute cardiovascular events [7] and higher healthcare costs [8]. Hypercholesterolemia is one of the top 10 costliest medical conditions in 2008 in the US adult population [9].

#### *1.1. Treatment Approaches*

Diet and lifestyle modifications with or before starting the cholesterol-lowering drugs are the primary line of treatment for hypercholesterolemia [4]. Although emphasis is given to lifestyle modifications, a majority of people are required to take drugs to have an adequate reduction in LDL-C levels [10]. At present, the main drug class of choice for hypercholesterolemia is statins. Studies have suggested that statins can reduce the chance of heart attack and prevent consequent death by 30–40% and reduce LDL-C levels by 25–40%. Other alternatives to statins are fibrates, nicotinic acids, and cholesterol absorption inhibitors such as ezetimibe [4,10]. While these cholesterol-reducing drugs are generally considered safe, they are not free from side effects [10]. It is well established now that statin use is highly associated with adverse events and their manifestations such as myositis, myalgia, rhabdomyolysis, cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction [11]. In fact, statin use is also known to increase the risk of newonset diabetes from anywhere between 28–43% [12]. Many times, drugs such as statins and ezetimibe do not even reach the desired reduction in LDL levels, with residual CVD risk still persisting [13]. Adverse events associated with conventional treatments is also one of the reasons why a large percentage of the US population does not treat hypercholesterolemia despite being aware of the condition [14]. Such issues have prompted researchers to explore alternative/integrative treatment approaches and multiple new therapies are emerging in that area [13]. Complementary and alternative medicine (CAM) treatments have shown significant benefits among individuals with hypercholesterolemia [15]. One of the CAM therapies that has shown promising results for hypercholesterolemia is Ayurveda [16].
